Antagonism of BST2/Tetherin, a new restriction factor of respiratory syncytial virus, requires the viral NS1 protein.

Human respiratory syncytial virus (RSV) is an enveloped RNA virus and the leading viral agent responsible for severe pediatric respiratory infections worldwide. Identification of cellular factors able to restrict viral infection is one of the key strategies used to design new drugs against infection. Here, we report for the first time that the cellular protein BST2/Tetherin (a widely known host antiviral molecule) behaves as a restriction factor of RSV infection.

Methylation of ESCRT-III components regulates the timing of cytokinetic abscission.

Abscission is the final stage of cytokinesis, which cleaves the intercellular bridge (ICB) connecting two daughter cells. Abscission requires tight control of the recruitment and polymerization of the Endosomal Protein Complex Required for Transport-III (ESCRT-III) components. We explore the role of post-translational modifications in regulating ESCRT dynamics.

Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly.

Considerable progress has been made in understanding the molecular host-virus battlefield during SARS-CoV-2 infection. Nevertheless, the assembly and egress of newly formed virions are less understood. To identify host proteins involved in viral morphogenesis, we characterize the proteome of SARS-CoV-2 virions produced from A549-ACE2 and Calu-3 cells, isolated via ultracentrifugation on sucrose cushion or by ACE-2 affinity capture.

ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway.

Bone marrow stromal antigen 2 (BST2)/tetherin is a restriction factor that reduces HIV-1 dissemination by tethering virus at the cell surface. BST2 also acts as a sensor of HIV-1 budding, establishing a cellular antiviral state. The HIV-1 Vpu protein antagonizes BST2 antiviral functions via multiple mechanisms, including the subversion of an LC3C-associated pathway, a key cell intrinsic antimicrobial mechanism.

Unraveling membrane properties at the organelle-level with LipidDyn.

Cellular membranes are formed from different lipids in various amounts and proportions depending on the subcellular localization. The lipid composition of membranes is sensitive to changes in the cellular environment, and its alterations are linked to several diseases. Lipids not only form lipid-lipid interactions but also interact with other biomolecules, including proteins.

ATG9A supplies PtdIns4P to the autophagosome initiation site.

The identity of the platform supporting the initiation and formation of the nascent autophagosome, the phagophore, is not fully understood. Nucleation and expansion of the phagophore membrane requires a coordinated flux or activation of specific proteins and membrane lipids at the initiation site. The transmembrane protein ATG9A is essential for macroautophagy/autophagy and proposed to be an initiator of the phagophore by directing or facilitating the delivery of proteins and lipids to the initiation site.

ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIβ.

ATG9A is a multispanning membrane protein essential for autophagy. Normally resident in Golgi membranes and endosomes, during amino acid starvation, ATG9A traffics to sites of autophagosome formation. ATG9A is not incorporated into autophagosomes but is proposed to supply so-far-unidentified proteins and lipids to the autophagosome.

Contribution of the Cytoplasmic Determinants of Vpu to the Expansion of Virus-Containing Compartments in HIV-1-Infected Macrophages.

HIV-1 infection of macrophages leads to the sequestration of newly formed viruses in intracellular plasma membrane-connected structures termed virus-containing compartments (VCCs), where virions remain infectious and hidden from immune surveillance. The cellular restriction factor bone marrow stromal cell antigen 2 (BST2), which prevents HIV-1 dissemination by tethering budding viral particles at the plasma membrane, can be found in VCCs. The HIV-1 accessory protein Vpu counteracts the restriction factor BST2 by downregulating its expression and removing it from viral budding sites.

Membrane dynamics and organelle biogenesis-lipid pipelines and vesicular carriers.

Discoveries spanning several decades have pointed to vital membrane lipid trafficking pathways involving both vesicular and non-vesicular carriers. But the relative contributions for distinct membrane delivery pathways in cell growth and organelle biogenesis continue to be a puzzle. This is because lipids flow from many sources and across many paths via transport vesicles, non-vesicular transfer proteins, and dynamic interactions between organelles at membrane contact sites.

Centriolar Satellites Control GABARAP Ubiquitination and GABARAP-Mediated Autophagy.

Autophagy maintains cellular health and homeostasis during stress by delivering cytosolic material captured by autophagosomes to lysosomes for degradation. Autophagosome formation is complex: initiated by the recruitment of autophagy (Atg) proteins to the formation site, it is sustained by activation of Atg proteins to allow growth and closure of the autophagosome. How Atg proteins are translocated to the forming autophagosome is not fully understood.

TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic.

Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain-containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11-positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi-subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14.

Activation of ULK Kinase and Autophagy by GABARAP Trafficking from the Centrosome Is Regulated by WAC and GM130.

Starvation-induced autophagy requires activation of the ULK complex at the phagophore. Two Golgi proteins, WAC and GM130, regulate autophagy, however their mechanism of regulation is unknown. In search of novel interaction partners of WAC, we found that GM130 directly interacts with WAC, and this interaction is required for autophagy.

Species-specific impact of the autophagy machinery on Chikungunya virus infection.

Chikungunya virus (CHIKV) is a recently re-emerged arbovirus that triggers autophagy. Here, we show that CHIKV interacts with components of the autophagy machinery during its replication cycle, inducing a cytoprotective effect. The autophagy receptor p62 protects cells from death by binding ubiquitinated capsid and targeting it to autophagolysosomes.

Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines.

Mapping of Chikungunya virus interactions with host proteins identified nsP2 as a highly connected viral component.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has been responsible for an epidemic outbreak of unprecedented magnitude in recent years. Since then, significant efforts have been made to better understand the biology of this virus, but we still have poor knowledge of CHIKV interactions with host cell components at the molecular level. Here we describe the extensive use of high-throughput yeast two-hybrid (HT-Y2H) assays to characterize interactions between CHIKV and human proteins.

Calcineurin inhibitor-free GVHD prophylaxis with sirolimus, mycophenolate mofetil and ATG in Allo-SCT for leukemia patients with high relapse risk: an observational cohort study.

Certain leukemias have a high relapse risk even after allo-SCT, and GVHD prophylaxis with calcineurin inhibitors (CNIs) may interfere with a possible GVL effect. Therefore, we replaced CYA by sirolimus in patients with high relapse risk. In contrast to CNIs, sirolimus promotes the generation of regulatory T-cells and has potent antineoplastic activity.

Improvement of severe secondary hyperparathyroidism in dialysis patients by intravenous 1 alpha(OH) vitamin D3, oral CaCO3 and low dialysate calcium.

Seventeen patients (9 men, 8 women; aged 27 to 75 years) who were on chronic hemodialysis for 1 to 14 years were included in the study because they had severe hyperparathyroidism diagnosed by elevated plasma alkaline phosphatase and on plasma intact PTH levels more than twice the upper limit of normal. They had been previously treated with various combinations of oral calcium and/or Al(OH)3 as phosphate binders, oral 1 alpha(OH) vitamin D3 metabolites and a dialysate calcium concentration (DCa) of 1.6 to 1.

[One-year treatment of 43 chronic hemodialysis patients with recombinant human erythropoietin].

Twenty men and 23 women aged from 18 to 65 years, who had been under maintenance haemodialysis for 2 to 16 years and whose haematocrit had been below 30 percent for at least 3 months received recombinant human erythropoietin intravenously at the end of each session for one year. Anaemia was corrected in all patients, the delay in response to each dosage variation being about 4 weeks. The necessary maintenance dosage ranged from 96 to 240 u/kg/week.

[Persistent or recurrent hyperparathyroidism in periodically hemodialyzed patients. Value of preoperative cervical ultrasonography. 6 cases].

In 2 cases of recurrent secondary hyperparathyroidism and 4 cases of persisting secondary hyperparathyroidism observed in patients treated by chronic haemodialysis, 8 hyperplastic parathyroid masses and 1 parathyroid adenoma, all located in the lower part of the neck, were removed after percutaneous ultrasonographic detection. There were 7 true positive and 1 unexplained false positive results. In 1 out of the 2 false negative results, the mass located behind the esophagus could not be detected because of the laryngotracheal gas.